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@ARTICLE{Direk:826053,
author = {Direk, Nese and Williams, Stephanie and Smith, Jennifer A.
and Ripke, Stephan and Air, Tracy and Amare, Azmeraw T. and
Amin, Najaf and Baune, Bernhard T. and Bennett, David A. and
Blackwood, Douglas H. R. and Boomsma, Dorret and Breen,
Gerome and Buttenschøn, Henriette N. and Byrne, Enda M. and
Børglum, Anders D. and Castelao, Enrique and Cichon, Sven
and Clarke, Toni-Kim and Cornelis, Marilyn C. and
Dannlowski, Udo and De Jager, Philip L. and Demirkan, Ayse
and Domenici, Enrico and van Duijn, Cornelia M. and Dunn,
Erin C. and Eriksson, Johan G. and Esko, Tonu and Faul,
Jessica D. and Ferrucci, Luigi and Fornage, Myriam and de
Geus, Eco and Gill, Michael and Gordon, Scott D. and Grabe,
Hans Jörgen and van Grootheest, Gerard and Hamilton, Steven
P. and Hartman, Catharina A. and Heath, Andrew C. and Hek,
Karin and Hofman, Albert and Homuth, Georg and Horn, Carsten
and Jan Hottenga, Jouke and Kardia, Sharon L. R. and
Kloiber, Stefan and Koenen, Karestan and Kutalik, Zoltán
and Ladwig, Karl-Heinz and Lahti, Jari and Levinson, Douglas
F. and Lewis, Cathryn M. and Lewis, Glyn and Li, Qingqin S.
and Llewellyn, David J. and Lucae, Susanne and Lunetta,
Kathryn L. and MacIntyre, Donald J. and Madden, Pamela and
Martin, Nicholas G. and McIntosh, Andrew M. and Metspalu,
Andres and Milaneschi, Yuri and Montgomery, Grant W. and
Mors, Ole and Mosley, Thomas H. and Murabito, Joanne M. and
Müller-Myhsok, Bertram and Nöthen, Markus M. and Nyholt,
Dale R. and O’Donovan, Michael C. and Penninx, Brenda W.
and Pergadia, Michele L. and Perlis, Roy and Potash, James
B. and Preisig, Martin and Purcell, Shaun M. and Quiroz,
Jorge A. and Räikkönen, Katri and Rice, John P. and
Rietschel, Marcella and Rivera, Margarita and Schulze,
Thomas G. and Shi, Jianxin and Shyn, Stanley and Sinnamon,
Grant C. and Smit, Johannes H. and Smoller, Jordan W. and
Snieder, Harold and Tanaka, Toshiko and Tansey, Katherine E.
and Teumer, Alexander and Uher, Rudolf and Umbricht, Daniel
and Van der Auwera, Sandra and Ware, Erin B. and Weir, David
R. and Weissman, Myrna M. and Willemsen, Gonneke and Yang,
Jingyun and Zhao, Wei and Tiemeier, Henning and Sullivan,
Patrick F.},
title = {{A}n {A}nalysis of {T}wo {G}enome-wide {A}ssociation
{M}eta-analyses {I}dentifies a {N}ew {L}ocus for {B}road
{D}epression {P}henotype},
journal = {Biological psychiatry},
volume = {82},
number = {5},
issn = {0006-3223},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2017-00322},
pages = {322-329},
year = {2017},
abstract = {BackgroundThe genetics of depression has been explored in
genome-wide association studies that focused on either major
depressive disorder or depressive symptoms with mostly
negative findings. A broad depression phenotype including
both phenotypes has not been tested previously using a
genome-wide association approach. We aimed to identify
genetic polymorphisms significantly associated with a broad
phenotype from depressive symptoms to major depressive
disorder.MethodsWe analyzed two prior studies of 70,017
participants of European ancestry from general and clinical
populations in the discovery stage. We performed a
replication meta-analysis of 28,328 participants. Single
nucleotide polymorphism (SNP)-based heritability and genetic
correlations were calculated using linkage disequilibrium
score regression. Discovery and replication analyses were
performed using a p-value-based meta-analysis. Lifetime
major depressive disorder and depressive symptom scores were
used as the outcome measures.ResultsThe SNP-based
heritability of major depressive disorder was 0.21 (SE =
0.02), the SNP-based heritability of depressive symptoms was
0.04 (SE = 0.01), and their genetic correlation was 1.001
(SE = 0.2). We found one genome-wide significant locus
related to the broad depression phenotype (rs9825823,
chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an
intron of the FHIT gene. We replicated this SNP in
independent samples (p = .02) and the overall meta-analysis
of the discovery and replication cohorts (1.0 ×
10–9).ConclusionsThis large study identified a new locus
for depression. Our results support a continuum between
depressive symptoms and major depressive disorder. A
phenotypically more inclusive approach may help to achieve
the large sample sizes needed to detect susceptibility loci
for depression.},
cin = {INM-1},
ddc = {570},
cid = {I:(DE-Juel1)INM-1-20090406},
pnm = {571 - Connectivity and Activity (POF3-571) / HBP - Human
Brain Project (284941)},
pid = {G:(DE-HGF)POF3-571 / G:(EU-Grant)284941},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000406938900010},
pubmed = {pmid:28049566},
doi = {10.1016/j.biopsych.2016.11.013},
url = {https://juser.fz-juelich.de/record/826053},
}